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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1552426
This article is part of the Research Topic Harnessing Big Data for Precision Medicine: Revolutionizing Diagnosis and Treatment Strategies View all 22 articles
Circulating cell-free DNA methylation analysis of pancreatic cancer patients for early noninvasive diagnosis
Provisionally accepted
Wenzhe Hu 1
Xudong Zhao 2* Nan Luo 1* Mengmeng Xiao 3* Feng Feng 1* Yuan An 1* Jianfei Chen 1* Long Rong 2* Yinmo Yang 4* Jirun Peng 1*- 1 Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- 2 Endoscopy Center, First Hospital, Peking University, Beijing, Beijing Municipality, China
- 3 Peking University People's Hospital, Beijing, Beijing Municipality, China
- 4 First Hospital, Peking University, Beijing, Beijing Municipality, China
Background: Aberrant hypermethylation of genomic DNA CpG islands (CGIs) is frequently observed in human pancreatic cancer (PAC). A plasma cell-free DNA (cfDNA) methylation analysis method can be utilized for the early and noninvasive detection of PAC. This study also aimed to differentiate PAC from other cancer types.We employed the methylated CpG tandem amplification and sequencing (MCTA-Seq) method, which targets approximately one-third of CGIs, on plasma samples from PAC patients (n = 50) and healthy controls (n = 52), as well as from cancerous and adjacent noncancerous tissue samples (n = 66). The method's efficacy in detecting PAC and distinguishing it from hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastric cancer (GC) was evaluated. Additionally, a methylation score and typing system for PAC was also established.We identified a total of 120 cfDNA methylation biomarkers, including IRX4, KCNS2, and RIMS4, for the detection of PAC in blood. A panel comprising these biomarkers achieved a sensitivity of 97% and 86% for patients in the discovery and validation cohorts, respectively, with a specificity of 100% in both cohorts. The methylation scoring and typing systems were clinically applicable. Furthermore, we identified hundreds of differentially methylated cfDNA biomarkers between PAC and HCC, CRC, and GC. Certain combinations of these markers can be used in a highly specific (approximately 100%) algorithm to differentiate PAC from HCC, CRC, and GC in blood.Our study identified cfDNA methylation markers for PAC, offering a novel approach for the early, noninvasive diagnosis of PAC.
Keywords: circulating cell-free DNA, DNA Methylation, Pancreatic Cancer, early noninvasive diagnosis, Hepatocellular Carcinoma, colorectal cancer, gastric cancer
Received: 28 Dec 2024; Accepted: 13 Feb 2025.
Copyright: © 2025 Hu, Zhao, Luo, Xiao, Feng, An, Chen, Rong, Yang and Peng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xudong Zhao, Endoscopy Center, First Hospital, Peking University, Beijing, Beijing Municipality, China
Nan Luo, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
Mengmeng Xiao, Peking University People's Hospital, Beijing, 100044, Beijing Municipality, China
Feng Feng, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
Yuan An, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
Jianfei Chen, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
Long Rong, Endoscopy Center, First Hospital, Peking University, Beijing, Beijing Municipality, China
Yinmo Yang, First Hospital, Peking University, Beijing, Beijing Municipality, China
Jirun Peng, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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